To reduce the incidence of neural tube defects, the US Food and Drug Administration (FDA) mandated folic acid fortification of flour and other grains beginning in 1998.1 Subsequent studies showed an overall increase in mean folic acid levels among US residents.2,3 Within a few years of this mandate, a decrease in the incidence of neural tube defects was noted in newborns.4 However, longer-term benefits of folic acid fortification for disease prevention,5 including multiple cancers,6-8 remain to be documented. Animal studies suggest that modest supplementation can reduce carcinogenesis. On the other hand, high doses of folic acid may speed cell division and increase tumor progression in preneoplastic lesions.9,10 Better understanding of time frame and dosage is key to balancing risk and benefits.